A Retrospective Evaluation of PD-L1 Expression and Heterogeneity in Early-Stage Non-Small Cell Lung Cancer (REPLICA)

Immune checkpoint inhibitors have improved survival in patients with non-small cell lung cancer (NSCLC). Whilst PD-L1 expression is a useful predictive biomarker, data on concordance of expression between primary tumor and nodal metastases in the surgical setting are sparse.

We assessed PD-L1 expression in paired primary tumor and involved lymph node samples from 451 consecutive patients with stage IIB-IIIB NSCLC who underwent curative lung resection and lymphadenectomy at our institution between 2009 and 2018, to assess intertumor heterogeneity. Clinical records were examined to determine survival outcomes, and relationship to PD-L1 expression was explored.

Using PD-L1 expression categories of < 1%, 1% to 49% and ≥ 50% there was heterogeneity of PD-L1 expression between the primary and corresponding lymph node metastases in 24% of cases with only moderate positive correlation (Spearman's coefficient 0.7). 46% of early-stage primary tumors expressed PD-L1, although only 11% demonstrated a high (> 50%) level. It was more common for PD-L1 expression to be higher in the primary tumor than its metastatic lymph node than the converse. PD-L1 expression irrespective of site, had no significant impact on disease-free or overall survival.

Our study confirms the heterogeneity of PD-L1 expression in early-stage NSCLC and suggests that a biopsy specimen from a single site may not be a comprehensive representation of PD-L1 expression. The proportion of tumours with high PD-L1 expression appears lower in early-stage NSCLC than in advanced disease.